A Phase I/II, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of ACE-86225106 as Monotherapy in Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 298
- 试验地点
- 27
- 主要终点
- Number of participants experiencing adverse events (AEs)/serious adverse events (SAEs)
研究概览
简要总结
The purpose of this study is to determine if the experimental treatment with poly-ADP ribose polymerase (PARP) inhibitor, ACE-86225106 is safe, tolerable and has anti-cancer activity in adult patients with advanced solid tumors.
详细描述
This study is a Phase I/II, open-label, multicentre study of ACE-86225106 administered orally in patients with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Provide written informed consent;
- •Advanced solid tumors, difficult to treat or intolerant to standard treatment, suitable for investigational treatment;
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •Has a life expectancy of at least 3 months;
- •Has measurable disease per RECIST 1.1, castration-resistant prostate Ccancer (CRPC) patients can be assessed according to PCWG3;
- •Adequate organ function and bone marrow function;
- •Can provide tumor specimens and blood samples for Homologous Recombination Deficiency (HRD)/ Homologous Recombination Repair (HRR) related gene testing.
排除标准
- •Receiving any anti-cancer drugs, major surgery, extensive radiation therapy, or local radiation therapy within protocol-defined wash-out period;
- •Concomitant use of medications or herbal supplements known to be strong or moderate inhibitors or inducers of cytochrome P450 3A4 (CYP3A4);
- •Receiving continuous corticosteroid treatment with a dose of prednisone greater than 10 mg/day or an equivalent dose.
- •Receiving continuous treatment with prednisone at a dose of >10 mg/d or other corticosteroids at an equivalent dose for any reason.
- •Any previous treatment-related toxicities have not recovered, i.e., to ≤ Grade 1 (as evaluated by NCI-CTCAE v5), except alopecia and other Grade 2 toxicities that are deemed not to affect the conduct of the study, as assessed by the sponsor and the clinical investigator.
- •Spinal cord compression or brain metastases unless asymptomatic, treated and stable.
- •Severe cardiovascular disorders.
- •Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or with evidence suggesting possible MDS/AML.
- •Concomitant diseases or conditions that would preclude the absorption of the investigational product.
- •Active infections, or a known history of HIV infection, or a known active hepatitis B or C, or a known active tuberculosis.
- •Other malignancies that require treatment within 3 years prior to first dose of study investigational product.
- •Conditions with rapid deterioration during the screening period.
- •Known allergy or hypersensitivity to the investigational product or any of the excipients of the investigational product.
- •Has other medical conditions that at the discretion of investigator interfere with safety or efficacy evaluation, or affect treatment compliance.
研究组 & 干预措施
ACE-86225106 tablet
ACE-86225106 tablet monotherapy
干预措施: ACE-86225106 tablet (Drug)
结局指标
主要结局
Number of participants experiencing adverse events (AEs)/serious adverse events (SAEs)
时间窗: From time of information consent to 30 days post last dose, up to 3 years
Number of participants with incidence of adverse events and with serious adverse events including changes from baseline in laboratory parameters, vital signs, ECGs, and physical examination, etc.
The number of patients experiencing dose limiting toxicity (DLT), as defined in the protocol
时间窗: From the first dose of ACE-86225106 on Cycle 1 Day 1 up to and including the planned end of Cycle 1 (at the end of 28 days)
A DLT is defined as any toxicity events related to ACE-86225106 that occur from the first dose of study treatment until the planned end date of Cycle 1 (DLT assessment period), meeting the criteria specified in protocol.
Recommended Phase 2 dose (RP2D) and/or maximum tolerated dose (MTD)
时间窗: Up to 3 years
RP2D will be finally determined by the Safety Monitoring Committee (SMC) and sponsor based on all data from the dose escalation module and backfill module, as well as the exposure-response relationship evaluated (if available). MTD is defined as the maximum dose level at which ≤1 patient have DLTs during the DLT observation period, and it should be determined with 6 evaluable patients.
次要结局
- Objective Response Rate (ORR)(Up to 3 years)
- Duration of Response (DoR) and Time to Response (TTR)(Up to 3 years)
- Progression Free Survival (PFS)(Up to 3 years)
- Overall Survival (OS)(Up to 3 years)
- Pharmacokinetic (PK) parameters and Pharmacodynamic (PD) marker change(Up to 3 years)
- Serum tumor marker change: CA125, etc. (OC), prostatic specific antigen (PSA, prostate cancer) decreased, and specific tumor markers for other tumor types may also be included (to be assessed by clinical investigators)(Up to 3 years)